Characterization of insulin crystalline form in isolated β-cell secretory granules.
Seiya AsaiJana MoravcováLenka ŽákováIrena SelicharováRomana HadravováAndrzej Marek BrzozowskiJiri NovacekJiří JiráčekPublished in: Open biology (2022)
Insulin is stored in vivo inside the pancreatic β-cell insulin secretory granules. In vitro studies have led to an assumption that high insulin and Zn 2+ concentrations inside the pancreatic β-cell insulin secretory granules should promote insulin crystalline state in the form of Zn 2+ -stabilized hexamers. Electron microscopic images of thin sections of the pancreatic β-cells often show a dense, regular pattern core, suggesting the presence of insulin crystals. However, the structural features of the storage forms of insulin in native preparations of secretory granules are unknown, because of their small size, fragile character and difficult handling. We isolated and investigated the secretory granules from MIN6 cells under near-native conditions, using cryo-electron microscopic (Cryo-EM) techniques. The analysis of these data from multiple intra -granular crystals revealed two different rhomboidal crystal lattices. The minor lattice has unit cell parameters ( a ≃ b ≃ 84.0 Å, c ≃ 35.2 Å), similar to in vitro crystallized human 4Zn 2+ -insulin hexamer, whereas the largely prevalent unit cell has more than double c -axis ( a ≃ b ≃ c ≃ 96.5 Å) that probably corresponds to two or three insulin hexamers in the asymmetric unit. Our experimental data show that insulin can be present in pancreatic MIN 6 cell granules in a microcrystalline form, probably consisting of 4Zn 2+ -hexamers of this hormone.
Keyphrases
- type diabetes
- glycemic control
- single cell
- cell therapy
- induced apoptosis
- room temperature
- heavy metals
- stem cells
- big data
- signaling pathway
- machine learning
- high resolution
- oxidative stress
- adipose tissue
- endoplasmic reticulum stress
- artificial intelligence
- cell proliferation
- optical coherence tomography
- high speed
- atomic force microscopy
- solar cells
- electron transfer